梅花鹿鹿茸胶原酶解物的制备及活性研究
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摘要
本文通过优选采用水提法从梅花鹿鹿茸中分离提取出胶原,并通过蛋白酶对其进行水解,增强了胶原的溶解性,得到了鹿茸胶原酶解物(CSDV);采用薄层色谱、高效液相色谱、紫外光谱、红外光谱、圆二光谱现代谱学技术对CSDV的理化性质和蛋白结构组成进行了初步研究;对CSDV的药理活性进行筛选,并对其抗骨质疏松作用进行了药效学实验,最终以梅花鹿茸胶原为基源开发保健食品1种,并制定了相应的质量标准和操作规程。
1采用水提法与酶解法相结合,提取CSDV的工艺研究。
采用Folin-酚试剂法测量胶原蛋白含量,并以此为指标,考察了不同料液比(1:1,1:2,1:3,1:4,1:5)、不同提取时间(1 h,2 h,3 h,4 h,5 h)、不同提取次数(1,2,3,4,5次)三个因素对胶原提取率的影响,通过单因素考察和正交试验发现提取次数对提取率影响最大,提取时间其次,料液比对提取率影响不明显,确定了最佳提取条件,即:料液比1:3,提取4 h,提取5次。在此基础上,采用高效液相分子筛柱检测蛋白分子量,以胶原酶解后分子量为指标,通过单因素考察实验,筛选了酶解时间(0 h,0.5 h,1 h,2 h)和其与底物作用的比值(1:3000,1:5000,1:8000,1:10000)对胶原分子量的影响,优选胰蛋白酶最佳提取条件是酶与底物比为1:5000,酶解时间为2 h。验证试验证实,在料液比为1:3,提取次数为5次,提取时间为每次4 h,酶与底物比为1:5000,酶解时间为2 h条件下提取率最高。通过测试和计算,采用以上工艺得到鹿茸胶原蛋白平均收率为12.52%,平均蛋白含量为56.89%。
2采用现代分析技术手段对CSDV理化性质和蛋白结构组成进行初步研究。
采用SDS-聚丙烯酰胺凝胶电泳(SDS-PAGE),测定梅花鹿鹿茸胶原酶解物分子量,结果显示,CSDV分子量集中在31 kDa以下,与高效液相检测到的结果相符合;应用酸水解法,对CSDV氨基酸成分进行分析,分析结果显示在20种常见氨基酸中,含量最高的是甘氨酸、脯氨酸和丙氨酸,其中甘氨酸含量为32.10%,占了几乎1/3,脯氨酸含量15.50%,丙氨酸为13.87%,甲硫氨酸,酪氨酸和组氨酸含量较低,没有检测出含有胱氨酸,非常见氨基酸—羟脯氨酸的含量也非常高,为6.71%,这一结果符合胶原氨基酸含量特征;TLC薄层色谱检识CSDV与标准品在相同位置出现桃红色斑点;茚三酮显色反应呈蓝紫色;含水量检测结果显示CSDV含水量为8.24%;变温法分析了梅花鹿鹿茸胶原黏度随温度变化情况,结果显示鹿茸胶原溶液具有很高黏度,且黏度随温度升高逐渐降低,温度为20℃以下时,基本失去流动性,胶原酶解后,黏度迅速下降;紫外吸收光谱显示其在260 nm有最大吸收;红外光谱结果说明CSDV中没有新的化学键产生;圆二色谱分析结果显示CSDV中二级结构数量α-螺旋、β-折叠和无规卷曲数量分别为3.6%,42.7%和53.7%。
3对CSDV急性毒性进行了研究。
急性毒性试验表明, 20只小鼠按体重灌胃给予鹿茸胶原酶解物10 g?kg-1?d-1,每日2次,观察14 d。20只小鼠全部存活。说明CSDV属实际无毒级。
4对CSDV小鼠生长和性腺相关脏器的影响。
小鼠血清血糖及睾酮含量检测发现CSDV能够促进小鼠体重的增长速度,使小鼠性腺相关脏器前列腺-贮精囊、睾丸、提肛肌-海绵球肌重量增加,血液中睾酮含量增加,同时,胸腺重量增加,血糖含量下降。说明梅花鹿茸胶原酶解物能促进小鼠生长和性腺器官的发育,降低血液中葡萄糖含量。
5对CSDV抗炎免疫抗应激作用进行了研究。
急性特异性免疫实验结果表明,CSDV在0.2 g?kg-1剂量下对小鼠角叉菜胶引起的足肿胀有抑制作用,P﹤0.05;当剂量为0.5 g?kg-1和0.25 g?kg-1时对DNCB所致小鼠迟发型超敏反应有抑制作用,并可一定程度促进小鼠巨噬细胞吞噬功能;抗应激实验结果表明,剂量0.5 g?kg-1时,可延长小鼠存活时间;1.0 g?kg-1、0.5 g?kg-1和0.25 g?kg-1均可延长小鼠游泳时间,只有在1.0 g?kg-1和0.5 g?kg-1时差异明显。
6采用去势和维甲酸两种方法造模对CSDV防治骨质疏松症作用进行了研究。
对去势雌性大鼠骨质疏松症防治作用实验结果表明,与正常对照组比较,模型组大鼠骨密度降低(P<0.01),血清生化指标骨钙素(BGP)、碱性磷酸酶(ALP)、雌二醇(E2)、血清磷(S-P)、血清钙(S-Ca)指标变化均有统计学意义,骨生物力学指标明显改变:最大载荷、最大挠度、骨应变都减小或变弱,骨形态计量学指标骨小梁占视域面积百分数(TBV)减少、平均骨小梁间距(MTPS)明显增大、平均骨皮质厚度(MBCT)明显变大,说明造模成功;经CSDV治疗后,上述指标除E2、S-P、S-Ca、MBCT外均明显改善,剂量在0.4 g?kg-1时防治作用最显著。
对维甲酸致大鼠骨质疏松症防治作用试验结果表明,与对照组比较,模型组大鼠骨密度降低(P<0.01),血液生化骨转换指标S-Ca降低,骨组织静态计量学指标变化明显:骨小梁占视域面积百分数比正常对照组减少了近50%,骨量丢失明显,MTPS明显增大(P<0.001)、MTPT明显变窄(P<0.001)、MBCT明显变大(P<0.001),骨生物力学各项指标明显改变:最大载荷、最大挠度、骨应变减弱或变小,说明造模成功;经与CSDV干预组对比,上述指标都出现了明显的改善,骨密度增加(P<0.05),ALP降低,S-Ca、S-P升高,骨量明显增加,骨小梁形态发生逆转、数量明显增加、间距变窄等,综合比较剂量在0.2 g?kg-1时预防作用最显著。
7对CSDV抗辐射功效进行了研究。
从通过外周血白细胞计数实验、骨髓细胞DNA含量和骨髓细胞微核实验以及血常规检测等试验,针对鹿茸CSDV抗辐射功效做了系统评价。结果显示,CSDV只可显著降低由γ射线照射引起的骨髓细胞微核数增高。
8通过细胞实验检测了CSDV体外促细胞贴壁作用。
采用预先铺被CSDV方法,在6孔板中加入鹿茸胶原酶解物2 ml/孔。分别将3T3细胞,Vero细胞和分离得到大鼠乳鼠颅顶骨成骨细胞,接种于铺被胶原的培养板,培养24 h,结果显示CSDV在促进细胞贴壁方面作用不明显。
9梅花鹿茸“强筋壮骨”功效保健食品的开发。
以梅花鹿茸胶原为基源,在药效学实验基础上,开发出具有增加骨密度功效的保健食品——鹿茸胶原咀嚼片。对其生产工艺进行了研究,并进行了中试实验,制定了成品质量标准。
In this paper, we extracted collagen from sika deer antler with water at the optimal conditions and hydrolyzed by protease, which enhances the solubility of collagen.The methods such as thin-layer chromatography (TLC),high performance liquid chromatography (HPLC), ultraviolet spectrum (UV), infra-red spectrum(IR), circular dichroism spectrum (CD) and so on was used in studying on the physical-chemical properties of CSDV. We did the active test to the collagen. Osteoporosis rat models were established by ovariectomy and retinoid acid (RA).One kind of health food products was developed from sika deer antler collagen. And we lay down quality standard and operating procedure.
Here are the details:
1 Study on the optimum conditions of extraction of CSDV.
The collagen protein quantity was measured with folin-phenol reagent, and as a target, we want to know the influence of different liquid ratio (1:1,1:2,1:3,1:4,1:5), different extraction time (1 h , 2 h, 3 h, 4 h, 5 h), different extraction times (1,2,3,4,5 times) three factors on the extraction yield of collagen. That was compared by single factor and orthogonal experiment. It was found that the greatest impact on the extraction rate was extraction times, followed by extraction time, solid to liquid ratio of no significant effect on the extraction rate. The optimum extraction conditions namely: liquid ratio 1:3, extracted 5 times, 4 h per times.
By single factor experiments, we screen optimum hydrolysis conditions suchas the of the hydrolysis time (0 h, 0.5 h, 1 h, 2 h) and its and the role of the ratio of substrate (1:3000,1:5000,1:8000,1:10000) with the target molecular weight of collagen.Results were that optimal trypsin was enzyme and substrate is the ratio of 1:5000, hydrolysis time to 2 h. Validation tests confirmed that under the above conditions, the extraction ratio was 12.52 percent on average, and the average protein content was 56.89%.
2 Preliminary study on physical and chemical properties.
By SDS-polyacrylamide gel electrophoresis (SDS-PAGE), molecular weight of CSDV were measured .The result showed it under 31 kDa, consistent with the result of HPLC. Acid hydrolysis was applicated in amino acid composition analysis on CSDV.Result show that the highest content is glycin, nearly 1/3 in the CSDV, and there is 15.50% proline and 13.87% alanine of it. Unusual amino acids - ydroxyproline content was very high too, nearly 6.71%. This result is consistent with characteristics of collagen amino acids. TLC seized at the same position with the standard collagen spots appear. Ninhydrin color reaction was blue-violet. Water content of the test results showed 8.24% moisture content. The effect of viscosity with temperature changes was researched; the viscosity decreased rapidly when collagen was enzymolysised.The UVspectra, IR, CD spectra was used in researching the characters of sika deer antler collagen. UV absorption spectra showed its maximum absorption at 260 nm,α-helix,β-fold and the number of random coil were 3.6%, 42.7% and 53.7% analyzed by CD.
3 Acute toxicity of CSDV was studied.
The acute oral toxicity test for this disinfectant indicated that it belonged to practically non-toxic grade.
4 Growth and development effects of CSDV on gonadal related organs.
Serum glucose and testosterone levels detected CSDV can contribute to weight gain in mice, And the weight of relevant organs of mouse prostate glands - the seminal vesicles, testes, levator ani muscles - sponge ball muscle increased, blood testosterone increased, Meanwhile, the thymus weight increased, blood glucose decreased.
5 Anti-inflammatory, immune and anti-stress effects of CSDV.
The anti-inflammatory, immune and anti-stress effect was obvious. Experimental results show that foot swelling caused by carrageenin in mice inhibition by CSDV in 0.2 g?kg-1, P<0.05; dinitrochlorobenzene induced delayed-type hypersensitivity was inhibited when the dose of 0.5 g?kg-1 and 0.25 g?kg-1, and may to some extent to promote macrophage phagocytosis. Anti-stress test results show that when the dose on 0.5 g?kg-1 survival time lengthen; and on 1.0 g?kg-1, 0.5 g?kg-1 and 0.25 g?kg-1 can extend the swimming time, but only 1.0 g?kg-1 and 0.5 g?kg-1 significantly different.
6 Prevention and therapeutic effects of CSDV on osteoporosis in rats.
To evaluate the preventive and therapeutic effects of the collagen extracted from Sika deer velvet (CSDV) on osteoporosis in ovariectomized rats. Compared with the ovariectomized group, CSDV markedly improve bone mineral density (BMD) and bone weight in ovariectomized rats, regulate the ALP and BGP in serum. There was marked difference in biomechanical properties and static histomorphometric indexes, such as Maximum load, Maximum deflection, bone stress, bone strain, TBV, MTPS, and MBCT between the collagen-treated groups and without.CSDV was found to play a role in the prevention and treatment of osteoporosis in ovariectomized rats.
The results of the study on prevention and therapeutic effects of CSDV on osteoporosis in rats by retinoic acid was similary with that in ovarectomized rats.
7 Anti radiation effects of CSDV was researched.
Results show that CSDV can only reduce the number of micronuclei bone marrow cells caused byγ-ray irradiation.
8 Study on promoting cell adhesion in vitro effects of CSDV.
The results of the experiments in vitro showed that there no effect on the cell adhesion in vitro.
9 One kind of health food was produced basis on the sika deer antler.
The chewable of CSDV was produced, and the quality standard was researching.
1采用水提法与酶解法相结合,提取CSDV的工艺研究。
采用Folin-酚试剂法测量胶原蛋白含量,并以此为指标,考察了不同料液比(1:1,1:2,1:3,1:4,1:5)、不同提取时间(1 h,2 h,3 h,4 h,5 h)、不同提取次数(1,2,3,4,5次)三个因素对胶原提取率的影响,通过单因素考察和正交试验发现提取次数对提取率影响最大,提取时间其次,料液比对提取率影响不明显,确定了最佳提取条件,即:料液比1:3,提取4 h,提取5次。在此基础上,采用高效液相分子筛柱检测蛋白分子量,以胶原酶解后分子量为指标,通过单因素考察实验,筛选了酶解时间(0 h,0.5 h,1 h,2 h)和其与底物作用的比值(1:3000,1:5000,1:8000,1:10000)对胶原分子量的影响,优选胰蛋白酶最佳提取条件是酶与底物比为1:5000,酶解时间为2 h。验证试验证实,在料液比为1:3,提取次数为5次,提取时间为每次4 h,酶与底物比为1:5000,酶解时间为2 h条件下提取率最高。通过测试和计算,采用以上工艺得到鹿茸胶原蛋白平均收率为12.52%,平均蛋白含量为56.89%。
2采用现代分析技术手段对CSDV理化性质和蛋白结构组成进行初步研究。
采用SDS-聚丙烯酰胺凝胶电泳(SDS-PAGE),测定梅花鹿鹿茸胶原酶解物分子量,结果显示,CSDV分子量集中在31 kDa以下,与高效液相检测到的结果相符合;应用酸水解法,对CSDV氨基酸成分进行分析,分析结果显示在20种常见氨基酸中,含量最高的是甘氨酸、脯氨酸和丙氨酸,其中甘氨酸含量为32.10%,占了几乎1/3,脯氨酸含量15.50%,丙氨酸为13.87%,甲硫氨酸,酪氨酸和组氨酸含量较低,没有检测出含有胱氨酸,非常见氨基酸—羟脯氨酸的含量也非常高,为6.71%,这一结果符合胶原氨基酸含量特征;TLC薄层色谱检识CSDV与标准品在相同位置出现桃红色斑点;茚三酮显色反应呈蓝紫色;含水量检测结果显示CSDV含水量为8.24%;变温法分析了梅花鹿鹿茸胶原黏度随温度变化情况,结果显示鹿茸胶原溶液具有很高黏度,且黏度随温度升高逐渐降低,温度为20℃以下时,基本失去流动性,胶原酶解后,黏度迅速下降;紫外吸收光谱显示其在260 nm有最大吸收;红外光谱结果说明CSDV中没有新的化学键产生;圆二色谱分析结果显示CSDV中二级结构数量α-螺旋、β-折叠和无规卷曲数量分别为3.6%,42.7%和53.7%。
3对CSDV急性毒性进行了研究。
急性毒性试验表明, 20只小鼠按体重灌胃给予鹿茸胶原酶解物10 g?kg-1?d-1,每日2次,观察14 d。20只小鼠全部存活。说明CSDV属实际无毒级。
4对CSDV小鼠生长和性腺相关脏器的影响。
小鼠血清血糖及睾酮含量检测发现CSDV能够促进小鼠体重的增长速度,使小鼠性腺相关脏器前列腺-贮精囊、睾丸、提肛肌-海绵球肌重量增加,血液中睾酮含量增加,同时,胸腺重量增加,血糖含量下降。说明梅花鹿茸胶原酶解物能促进小鼠生长和性腺器官的发育,降低血液中葡萄糖含量。
5对CSDV抗炎免疫抗应激作用进行了研究。
急性特异性免疫实验结果表明,CSDV在0.2 g?kg-1剂量下对小鼠角叉菜胶引起的足肿胀有抑制作用,P﹤0.05;当剂量为0.5 g?kg-1和0.25 g?kg-1时对DNCB所致小鼠迟发型超敏反应有抑制作用,并可一定程度促进小鼠巨噬细胞吞噬功能;抗应激实验结果表明,剂量0.5 g?kg-1时,可延长小鼠存活时间;1.0 g?kg-1、0.5 g?kg-1和0.25 g?kg-1均可延长小鼠游泳时间,只有在1.0 g?kg-1和0.5 g?kg-1时差异明显。
6采用去势和维甲酸两种方法造模对CSDV防治骨质疏松症作用进行了研究。
对去势雌性大鼠骨质疏松症防治作用实验结果表明,与正常对照组比较,模型组大鼠骨密度降低(P<0.01),血清生化指标骨钙素(BGP)、碱性磷酸酶(ALP)、雌二醇(E2)、血清磷(S-P)、血清钙(S-Ca)指标变化均有统计学意义,骨生物力学指标明显改变:最大载荷、最大挠度、骨应变都减小或变弱,骨形态计量学指标骨小梁占视域面积百分数(TBV)减少、平均骨小梁间距(MTPS)明显增大、平均骨皮质厚度(MBCT)明显变大,说明造模成功;经CSDV治疗后,上述指标除E2、S-P、S-Ca、MBCT外均明显改善,剂量在0.4 g?kg-1时防治作用最显著。
对维甲酸致大鼠骨质疏松症防治作用试验结果表明,与对照组比较,模型组大鼠骨密度降低(P<0.01),血液生化骨转换指标S-Ca降低,骨组织静态计量学指标变化明显:骨小梁占视域面积百分数比正常对照组减少了近50%,骨量丢失明显,MTPS明显增大(P<0.001)、MTPT明显变窄(P<0.001)、MBCT明显变大(P<0.001),骨生物力学各项指标明显改变:最大载荷、最大挠度、骨应变减弱或变小,说明造模成功;经与CSDV干预组对比,上述指标都出现了明显的改善,骨密度增加(P<0.05),ALP降低,S-Ca、S-P升高,骨量明显增加,骨小梁形态发生逆转、数量明显增加、间距变窄等,综合比较剂量在0.2 g?kg-1时预防作用最显著。
7对CSDV抗辐射功效进行了研究。
从通过外周血白细胞计数实验、骨髓细胞DNA含量和骨髓细胞微核实验以及血常规检测等试验,针对鹿茸CSDV抗辐射功效做了系统评价。结果显示,CSDV只可显著降低由γ射线照射引起的骨髓细胞微核数增高。
8通过细胞实验检测了CSDV体外促细胞贴壁作用。
采用预先铺被CSDV方法,在6孔板中加入鹿茸胶原酶解物2 ml/孔。分别将3T3细胞,Vero细胞和分离得到大鼠乳鼠颅顶骨成骨细胞,接种于铺被胶原的培养板,培养24 h,结果显示CSDV在促进细胞贴壁方面作用不明显。
9梅花鹿茸“强筋壮骨”功效保健食品的开发。
以梅花鹿茸胶原为基源,在药效学实验基础上,开发出具有增加骨密度功效的保健食品——鹿茸胶原咀嚼片。对其生产工艺进行了研究,并进行了中试实验,制定了成品质量标准。
In this paper, we extracted collagen from sika deer antler with water at the optimal conditions and hydrolyzed by protease, which enhances the solubility of collagen.The methods such as thin-layer chromatography (TLC),high performance liquid chromatography (HPLC), ultraviolet spectrum (UV), infra-red spectrum(IR), circular dichroism spectrum (CD) and so on was used in studying on the physical-chemical properties of CSDV. We did the active test to the collagen. Osteoporosis rat models were established by ovariectomy and retinoid acid (RA).One kind of health food products was developed from sika deer antler collagen. And we lay down quality standard and operating procedure.
Here are the details:
1 Study on the optimum conditions of extraction of CSDV.
The collagen protein quantity was measured with folin-phenol reagent, and as a target, we want to know the influence of different liquid ratio (1:1,1:2,1:3,1:4,1:5), different extraction time (1 h , 2 h, 3 h, 4 h, 5 h), different extraction times (1,2,3,4,5 times) three factors on the extraction yield of collagen. That was compared by single factor and orthogonal experiment. It was found that the greatest impact on the extraction rate was extraction times, followed by extraction time, solid to liquid ratio of no significant effect on the extraction rate. The optimum extraction conditions namely: liquid ratio 1:3, extracted 5 times, 4 h per times.
By single factor experiments, we screen optimum hydrolysis conditions suchas the of the hydrolysis time (0 h, 0.5 h, 1 h, 2 h) and its and the role of the ratio of substrate (1:3000,1:5000,1:8000,1:10000) with the target molecular weight of collagen.Results were that optimal trypsin was enzyme and substrate is the ratio of 1:5000, hydrolysis time to 2 h. Validation tests confirmed that under the above conditions, the extraction ratio was 12.52 percent on average, and the average protein content was 56.89%.
2 Preliminary study on physical and chemical properties.
By SDS-polyacrylamide gel electrophoresis (SDS-PAGE), molecular weight of CSDV were measured .The result showed it under 31 kDa, consistent with the result of HPLC. Acid hydrolysis was applicated in amino acid composition analysis on CSDV.Result show that the highest content is glycin, nearly 1/3 in the CSDV, and there is 15.50% proline and 13.87% alanine of it. Unusual amino acids - ydroxyproline content was very high too, nearly 6.71%. This result is consistent with characteristics of collagen amino acids. TLC seized at the same position with the standard collagen spots appear. Ninhydrin color reaction was blue-violet. Water content of the test results showed 8.24% moisture content. The effect of viscosity with temperature changes was researched; the viscosity decreased rapidly when collagen was enzymolysised.The UVspectra, IR, CD spectra was used in researching the characters of sika deer antler collagen. UV absorption spectra showed its maximum absorption at 260 nm,α-helix,β-fold and the number of random coil were 3.6%, 42.7% and 53.7% analyzed by CD.
3 Acute toxicity of CSDV was studied.
The acute oral toxicity test for this disinfectant indicated that it belonged to practically non-toxic grade.
4 Growth and development effects of CSDV on gonadal related organs.
Serum glucose and testosterone levels detected CSDV can contribute to weight gain in mice, And the weight of relevant organs of mouse prostate glands - the seminal vesicles, testes, levator ani muscles - sponge ball muscle increased, blood testosterone increased, Meanwhile, the thymus weight increased, blood glucose decreased.
5 Anti-inflammatory, immune and anti-stress effects of CSDV.
The anti-inflammatory, immune and anti-stress effect was obvious. Experimental results show that foot swelling caused by carrageenin in mice inhibition by CSDV in 0.2 g?kg-1, P<0.05; dinitrochlorobenzene induced delayed-type hypersensitivity was inhibited when the dose of 0.5 g?kg-1 and 0.25 g?kg-1, and may to some extent to promote macrophage phagocytosis. Anti-stress test results show that when the dose on 0.5 g?kg-1 survival time lengthen; and on 1.0 g?kg-1, 0.5 g?kg-1 and 0.25 g?kg-1 can extend the swimming time, but only 1.0 g?kg-1 and 0.5 g?kg-1 significantly different.
6 Prevention and therapeutic effects of CSDV on osteoporosis in rats.
To evaluate the preventive and therapeutic effects of the collagen extracted from Sika deer velvet (CSDV) on osteoporosis in ovariectomized rats. Compared with the ovariectomized group, CSDV markedly improve bone mineral density (BMD) and bone weight in ovariectomized rats, regulate the ALP and BGP in serum. There was marked difference in biomechanical properties and static histomorphometric indexes, such as Maximum load, Maximum deflection, bone stress, bone strain, TBV, MTPS, and MBCT between the collagen-treated groups and without.CSDV was found to play a role in the prevention and treatment of osteoporosis in ovariectomized rats.
The results of the study on prevention and therapeutic effects of CSDV on osteoporosis in rats by retinoic acid was similary with that in ovarectomized rats.
7 Anti radiation effects of CSDV was researched.
Results show that CSDV can only reduce the number of micronuclei bone marrow cells caused byγ-ray irradiation.
8 Study on promoting cell adhesion in vitro effects of CSDV.
The results of the experiments in vitro showed that there no effect on the cell adhesion in vitro.
9 One kind of health food was produced basis on the sika deer antler.
The chewable of CSDV was produced, and the quality standard was researching.
引文
[1]邓明鲁.中国动物药资源[M],北京:中国中医药出版社,第1版,2007:323-325;
[2]林鹤,曲晓波,王露菲,等.动物药整理研究(一)鹿茸,吉林中医药[J],2009,(1):50
[3]王本祥.鹿茸的研究[M].长春.吉林科学技术出版社1993:96-105
[4]严铭铭.人参鹿茸中蛋白多肽的纯化及活性研究[D].长春中医药大学,2007:5
[5]王玉.鹿茸化学成分的研究进展[J].吉林中医药,2006,26(12):73-75
[6]孟宪贞,程晓薇,陈力强.冷冻干燥与传统加工法制得的鹿茸化学成分分析极其比较研究[J],中国药房,1997,(8):3:110
[7]高士贤,中国动物药誌[M],吉林科学技术出版社,1996.10,963-976
[8]楼小红,陈建真.鹿茸中水溶性蛋白含量的测定[J].中国中医药科技,2003,10(1):31
[9]杨若明,张经华,张林源,等.麋鹿茸、马鹿茸和梅花鹿茸营养成分的分析比较研究[J],广东微量元素科学,2000,(7):12:47-51
[10]范玉琳,邢增涛,卫功庆,等.鹿茸蛋白的提取分离及其抗肿瘤活性[J].经济动物学报,1998;2(1):27-30
[11]周秋丽,郭颖洁.鹿茸多肤促进软骨和成骨样细胞增殖及骨折愈合[J].中国药理学报, 1999;20(3):279-282
[12]周秋丽,刘永强,王颖.梅花鹿茸和马鹿茸多肤化学性质及生物活性比较[J].中国中药杂志,2001;26(10):699-702
[13]周秋丽.鹿茸生长素药理作用的研究[J].中国药理学报,1997;11(5):16-19
[14]郭颖杰.鹿茸多肽对骨、软骨细胞增殖的实验研究[J].中国生化药物杂志,1998,19 (2) :74～75
[15]霍玉书,霍虹.鹿茸神经生长因子活性及促分化作用的研究[J].中药新药与临床药理, 1997;6(8):79-81
[16]张志强.鹿茸多肤的抗炎作用[J].中国药理学报,1994;15(3):282-284
[17]林冬云,鹿茸中活性多肽的研究[D],福州大学2004:6
[18]董万超,张秀莲,刘春华等.梅花鹿茸多肽新成分的提取分离及其生物学效应研究[J],特产研究,2000,2:7~10
[19]唐任能,赵雨,孙晓迪,等.梅花鹿鹿茸、鹿脱盘及鹿骨水溶性总蛋白比较研究[J],吉林中医药,2008,28(4):295-296
[20] Karpos,E.,Molnar,A.,Papp.,etal,Expression pattern of matrilins and other extracellular matrilins proteins characterize distinct stages of cell differentiation during antler development[J]. Matrix Biol,2005;24(2):124-135
[21] Barling,P.M.,Liu,H.,Matich,J.,et al. Expression of PTH/PTHrP receptor in growing red deer antler[J],Cell Biol lnt,2004;28(10):661-673
[22] Feng,J.Q.,Chen,D.,Esparza,J.,et al.Deer antler issue contains two types of bone morphogenetic protein 4 Mrna transcripts[J]. Biochim Biophys Acta ,1995;1263(2):163-168
[23] Feng,J.Q.,Chen,D.,Ghosh-Choudhury,N.,et al.Bone morphogenetic protein 2 transcripts in rapidly developing deer antler tissue contain an extended 5’non-coding region arising from a distal promoter[J].Biochim Biophys Acta,1997;1350(1):47-52
[24]王秋玉,王本祥.论鹿茸生长因子[J].中医药学报,2000,28(6):10-12
[25]崔昊震,尹明浩.鹿茸生长因子研究现状[J],延边大学医学学报,2006,3,29(1):70-72
[26] Ko,K.M.,Yip,T.T.,Tsao,S.W.,etal.Epidermal growth factor from deer(Cervus elaphus)submaxillary gland and velvet antler.GenComp Endocrinol[J], 1986;63(3):431-440
[27]李和平.中国茸鹿品种的鹿茸化学成分[J].东北林业大学学报,2003,7,31:(4)26-28
[28]杨秀伟,服部征雄,金子周司,等.日本生药学会第34回年会,1988:149~1535
[29]杨秀伟.花鹿茸、马鹿茸碱基成分的HPLC定量分析和其MA活性抑制作用[J].中草药,1995,26(l):17~19
[30]李继海,梅花鹿茸活性成分提取分离、功能评价及功能食品研究[D],中国农业大学,2005.4
[31]苗传风.梅花鹿茸磷脂和脂肪酸组成研究[J],特产研究1990,(3):48
[32]范玉琳.鹿茸化学成分研究的进展[J].中成药研究,1980,(1):23
[33]袁娟丽.鹿茸、麋鹿茸的化学和药理作用研究新进展[J] .江西中医学院学报,2003 ,6(15) ,2 :79～80
[34]杨秀伟,白云鹏.马鹿茸化学成分的研究[J] .中草药,1994 ,25(5) :229.
[35]龙远德,张惠祥,孙允秀.鹿茸中几种醚溶性成分的分离与鉴定[J].吉林大学自然科学学报. 1991(1) :1.
[36]高越,尹一子,李子健等.鹿茸中神经节苷脂的成分研究[J],吉林医学,2004,25(12):37-38
[37]熊和丽,杨鸣琦,杨萍等.梅花鹿鹿茸蛋白聚糖的提取与分离[J],西北农业学报,2007,16(4):80-82,91
[38]楼小红.吴巧凤.鹿茸中总糖的含量测定[J].中国药业,2003,12(2):57.
[39]蒋挺大.胶原与胶原蛋白[M],北京:化学工业出版社,第1版,2006:1-3;91-93;115-119
[40] Suttie,J.M.,et al. Velvet antler: A literature review. Batchelder[J],H.J.Health Supplement Retailer,1999;5:40-51
[41]王岩,金淑莉,陈晓光.鹿茸胶囊抗炎镇痛作用的研究[J].吉林中医药,2003,23(6):48
[42]刘青云.中药药理学[M],北京:人民卫生出版社,第二版,2002.2:258-260
[43]张红梅.人参与鹿茸配伍的作用机理研究[J],中医药学刊,2001,19(6):572
[44] Zheng,Z..Analysis on the therapeutic effect of combined use of acupuncture and mediation in 297 cases of male sterility[J].Jtradit Chin Med,1997;17(3):190-193
[45]楚立,张建平,李春花,等.H.S.B口服液的药理学研究[J].河北中医学院学报,1994;9(3):25-26
[46]刘筱茂.生津丹治疗男性不育104例[J],陕西中医学院学报,2000;23(2):35-36
[47]张红梅.人参与鹿茸配伍对肾阳虚大鼠生殖机能影响的实验研究[D].辽宁中医学院,2002.5
[48]洪文.针刺和鹿茸精穴位注射治疗肾阳虚男性不育症临床研究,广州中医药大学2002.6
[49]毋英杰,周丹,韩大庆等.诱发生长的雌鹿茸与雄鹿茸药理活性比较[J],特产研究,1996,(1):11-13
[50]何刚.鹿茸的药理作用与临床应用的研究进展[J].延边医学院学报,1992;(3):231-234
[51]楼一层,许健,程桃英.参茸百补胶囊的药效学研究[J],湖北中医学院学报,2003,5(2):23-24
[52] Wang Benxiang,Chen Xiaoguang. Inhibitory effect of hypoxanthine on monoamine oxidase activity.Acta Phamaceutica Sinica[J]. 1989:36(8):2-5.
[53]贺玉琢编译.汉方药对小鼠颌下腺生理活性物质的诱导作用及其作用机理[J],国外医学中国中药分册,1998,20(1):16-19
[54]许荔新,陈晓光.鹿茸口服液促进RNA和蛋白质合成作用的研究[J],中药药理与临床,2003;19(3)19-20
[55] Wang Benxiang,Chen Xiaoguang,et al.Influence of the active compounds isolated from pilose antler on syntheses of protein and RNA in mouse liver [J].Yao Xue Xue Bao,1990,25(5):321-325
[56] Wang Benxiang. Stimulating effects of deer antter extract on protein synthesis in senescence-accelerated mice in vivo [J]. Chem Pharm Bull, 1988,36(7):2593-2598
[57] Wang Benxiang,Chen Xiaoguang,et al. Effect of polyamines isolated from pilose antler (PASPA) on RNA polymerase activities in mouse liver [J].Yao Xue Xue Bao,1990;25(9):652-657
[58]杜中惠,曹际芬.鹿茸的临床应用及现代研究[J],中国药业,2000,9(1):53
[59]王岩,金淑莉,陈晓光.鹿茸胶囊耐缺氧和抗疲劳作用的实验研究[J].吉林中医药,2003;23(7):47-48
[60]姚克霓,补血生髓胶囊药理作用的研究[J],基层中药杂志,1996,10(3):35-36
[61]冯汉鸽,王喜云,张亚志.鹿茸不同部位的药理作用比较[J],时珍国药研究,1996,7(5):277-278
[62]孙晓波,周重楚.鹿茸精对机体免疫功能的影响[J].中成药研究,1986,21(8):636.
[63]乌恩,那顺·朝克图.鹿茸耐低氧作用的研究[J],内蒙古医学院学报,2007,29(3):192-193
[64]王羽竹,李子兰,贾瑞霞.牡丹江产鹿茸壮阳液药理实验研究[J].中国林副特产,2002,62(3):11-12
[65]关天颖,贾忠山,贾冬舒,等.特效生茸宝对小鼠造血功能和免疫功能的作用[J],中国兽医学报,199717(1):89-91
[66]王志华,赵文忠,李二秋.人参、鹿茸对体液免疫功能改善的研究[J],今日科技,2000(11):32-33
[67]唐巍然,于晓红,闻杰,等.鹿茸多糖对免疫功能低下模型小鼠细胞免疫功能的影响[J],中国中医药科技,2000,7(4):234.
[68]陈书明,聂向庭.鹿茸醇提物对白细胞减少小鼠模型腹腔吞噬细胞吞噬功能的影响[J],陕西中医学院学报,2000,1(1):4-5
[69]陈晓光,赵全成,邸琳,等.鹿茸糖肽对小鼠红细胞膜唾液酸酶的抑制作用[J],中国药理通讯,2003,20(3):24
[70]李召,鹿茸组分对人骨髓造血细胞体外增殖影响的研究[D],大连医科大学2006.6内科学
[71]关天颖,贾忠山,贾冬舒,等.特效生茸宝对小鼠造血功能和免疫功能的作用[J],中国兽医学报,199717(1):89-91
[72]王振宇,赵文静,李淑莲.鹿茸的药理作用及临床应用进展[J],中医药信息,2003,20(3):14
[73]葛迎春,李晨燕,任慧君,等.鹿茸提取物和人参皂甙对衰老细胞的琥珀酸脱氢酶和多糖含量的影响[J],特产研究,2001,(2):5-7.
[74]王立军,陈晓光,朴宪.鹿茸口服液对抗氧化酶的影响[J],中药药理与临床,2004,20(2):33-34
[75]关利新,初彦辉,郭艳芹,等.鹿茸抗衰老作用的研究[J],中国林副特产,1996,38(3):9-10
[76]王岩,陈晓光,金淑莉,等.鹿茸胶囊对青年及老年小鼠SOD活性的影响[J],中药实验药理,2003,31(4):22
[77]王本祥,陈晓光,徐惠波,等.次黄嘌呤-内源性单胺氧化酶(MAO)抑制剂样活性的研究[J],中药药理与临床,1996(1):9-14.
[78]陈书明,聂向庭.鹿茸醇提物抗氧化作用的实验研究,实验动物科学与管理[J],2000,17(1):22-24
[79]曲兆海,侯晓峰,刘景生.鹿茸对实验骨折愈合过程中TGF-β1的表达影响[J],中华实用中西医杂志,2003,3(16):707-709
[80]侯晓峰,李朝旭,刘景生.鹿茸对实验型骨折愈合中BMP-2表达的影响[J],辽宁中医杂志,2005,32(4):374-376
[81]周秋丽,王丽娟,郭颖杰,等.鹿茸多肽对实验性骨折的治疗作用及机理研究[J],白求恩医科大学学报,1999,25(5):586-588.
[82]郑洪新,任艳玲,杜松,等.活性鹿茸与热炸茸对去势大鼠骨质疏松症防治作用比较研究[J],中医药学刊,2004,22(4):616-619.
[83]陈晓超,柯李晶,陈躬瑞,等.鹿茸粗提液对大鼠成骨肉瘤细胞增殖的调节作用,中国中药杂志[J],2004,29(1):74-77
[84]姜廷良,霍海如,李兰芳,等.15中中西药物含药血清对大鼠成骨细胞增殖成熟的影响[J],中国骨质疏松杂志,2002,8(4):342-345.
[85]李娟,吴伟康,余克强.不同实验浓度补肾中药血清对人成骨细胞增殖及分化的促进作用[J],中国临床康复,2005,9(19):82-84
[86]张信岳,叶小弟,孟倩超,等.参茸强骨胶囊对皮质激素致大鼠骨质疏松症的保护作用[J],中国现代应用药学杂志,2003,20(4):265-268
[87]修忠标.鹿茸多肽对骨髓间质干细胞软骨分化生物学行为的影响[D],福建中医学院,中医骨伤科学,2005
[88]郭颖杰,周秋丽,刘平,等.鹿茸多肽对骨、软骨细胞增殖的实验研究[J],中国生化药物杂志,1998,19(2):74-76.
[89]侯建平,李丽静,王小丽,等.纳米鹿茸粗多肽对体外培养的软骨细胞代谢的影响[J],中国中医基础医学杂志,2006,12(7):555-556.
[90]修忠标,林建华.鹿茸多肽对人骨髓间质干细胞体外增殖的影响[J],福建中医学院学报,2005,15(1):34-37
[91]林建华,修忠标,吴朝阳,等.鹿茸多肽对兔骨髓间质干细胞体外增殖的影响[J],中华实验外科杂志,2005,22(7):827-828.
[92]林建华,修忠标,吴朝阳,等.鹿茸多肽对软骨表型化骨髓间充质干细胞凋亡的影响[J],中国修复重建外科杂志,2006,20(4):427-430
[93]修忠标,林建华,张春霞.鹿茸多肽对兔软骨细胞体外凋亡的影响[J],福建中医学院学报,2006,16(3):17-20.
[94]王利刚.中药鹿茸生长素对家兔关节软骨细胞代谢的影响[D],江西医学院,2001,骨科
[95]张志平,廖琦,李勇,等.鹿茸多肽对体外正常及凋亡软骨细胞代谢的影响[J],江西中医学院学报,2005,17(2):48-49
[96]陈东,孟晓婷.鹿茸多肽对胎大鼠脑神经干细胞体外诱导分化的实验研究[J].解剖学报,2004 ,6(3) :240– 242.
[97]翁梁,周秋丽.鹿茸多肽促进表皮和成纤维细胞增殖及皮肤创伤愈合[J].药学学报,2001 ,36(11) :817– 820.
[98]袁丽娟,谢金群.鹿茸、麋鹿茸的化学和药理作用研究新进展[J],江西中医学院学报,2003,15(2):79-80
[99]孟佳帆,王霞红,戎志毅,等.人源型可溶性胶原的研制[J],中国生物制品学杂志,2000,13(3):161-162
[100]刘秉慈.中国发明专利申请公开说明书.CN1081379A
[101]王新禾,张月娥,张锦生,等.人Ⅰ、Ⅲ型胶原的提取及其抗血清的制备[J],上海医科大学学报,1994,21(6):405-408.
[102]柴明胜,陈金国,叶仲贤,等.Ⅳ型胶原的提取纯化与抗血清的制备[J],陕西医学检验,1996,11(4):28-30
[103]姚敏捷,寇丽筠,王天成,等.人IV型胶原蛋白的提取及其单克隆抗体的制备与鉴定[J],细胞与分子免疫学杂志,1996,12(2):4-6
[104]李成章,樊明文.胚胎骨Ⅰ型胶原的提取与鉴定,生物化学与生物物理进展[J],1996,23(4):373-375
[105]范代娣,段明瑞,米钰,等.重组E.coli工程菌高密度培养生产人源型胶原蛋白,化工学报[J],2002,53(7):752-754
[106]王晓军,惠俊峰,米钰,等.重组类人胶原蛋白的分离纯化[J],中国生物制品学杂志,2003,16(4):212-214
[107]段明瑞,米钰,范代娣.重组人源型胶原蛋白基因工程菌补料分批发酵过程动力学研究化学反应工程与工艺[J],2002,18(3):238-243
[108]赵苍碧,黄玉东,李艳辉.从牛腱中提取胶原蛋白的研究[J],哈尔滨工业大学学报,2004,36(4)515-519.
[109]王由,李永岚,王维民.中国发明专利申请公开说明书.CN1407002A
[110]迪欧·弗兰[意大利].中国发明专利申请公开说明书.CN1110284A
[111]永井裕,藤本大三郎编著.胶原蛋白实验方法[M].刘平译.上海:上海中医学院出版社,1992.
[112]赵胜年.酶解鲜猪皮提取水解胶原蛋白的研究[J],食品工业科技,1998,(5):16-17
[113]李斯明,叶春婷,邹海燕,等.高纯度猪软骨Ⅱ型胶原的制备与检测[J],生物医学工程学杂志,2001,18(4):592-594
[114]林丁,刘兴明,李伟道,等.羊Ⅲ型前胶原放射免疫分析法的建立[J],生物技术,2002,12(2):33-34.
[115] KolodziejakaⅠ,Sikonski Z E,Njecikowaka C.Food Chem,1999,66(2):153-157.
[116]王瑾晔,董健.深海鱼皮组织工程用胶原蛋白和制备方法,中国发明专利申请公开说明书.NC1382806A
[117]鸿巢章二,桥本周久编.水产利用化学.郭晓峰,邹胜祥译.北京:农业出版社,1992
[118]郝林华,李八方.中国水产科学,1999,6(2):18-21
[119]方子季,梁东升,袁锦华.罗氏海盘车明胶代血浆的制备方法,中国发明专利申请审定说明书.CN1015776B.
[120]刘敬,许增禄,徐雁英,等.绝经后骨质疏松症病人Ⅰ型胶原的变化[J],解剖学报,2003,34(5):491-495
[121] Charles P, Mosekilde L,Risteli L, et al. Assessment of bone remodeling using biochemical indicators of type I collagen synthesis and degredation: relation to calcium kinetics[J].Bone Miner,1994, 24:81~94.
[122] Gertz BJ, Shao P, Hanson DA, et al. Monitoring bone resorption in early postmenopausal women by an immunoassay for crosslinked collagen peptides in wine[J].J Bone Min Res,1994,9:135~141.
[123] Fledelins C,Riis BJ, Overgaard K, et al. The diagnostic validity of urinary free pyridinolines to identify women at risk of osteoporosis[J]. Calcif Tissue Int,1994, 54:381~384.
[124] Cosman F, Nieves J, Wilkinson C,et al. Bone density change and biochemical indices of skeletal turnover[J].Calcif Tissue Int,1996, 58:236~243.
[125] Hoshino H, Takahashi M, kushida K,et al. Urinary encretion of type I collagen degradation products in healthywomen and osteoporotic patients with ventebral and hip fractures[J].Calcif Tissue Int,1998,62:36~39.
[126]李彦春,程宝箴,靳立强.胶原蛋白的应用[J].皮革化工,2002, 19(3):10-14.
[127]李彦春,靳立强,危东发,等.酶法提取牛皮胶原蛋白的研究[J].中国皮革, 2002, 31(2):6-9.
[128] Olsen D, Yang C, Bodo M, et al. Recombinant collagen and gelatin for drug delivery[J]. Adv Drug Deliv Rev, 2003, 55(12):1547-1567.
[129]林崇韬,文胡实,孙宏晨,等.乙酸溶解-酶消化法制备医用胶原膜[J].吉林大学学报(医学版), 2004, 30(1):75-78.
[130]李贺,刘白玲,陈华林,等.酶法提取猪皮胶原及其结构表征[J].中国皮革, 2002,31(23):14-16.
[131] NokelainenM, TuH, Vuorela A , et al. High-level production of human typeⅠcollagen in the yeast Pichia pastoris[J].Yeast, 2001,18(9):797-806.
[132] Friess W. Collagen-biomaterial for drug delivery[J]. Eur Jpharm Biopharm, 1998, 45(2): 113-136.
[133] Maeda M, KadotaK, Kajihara M, et al. Sustained release of human growth hormone(Hgh) from collagen film and evaluation of effect on wound healing in db/db mice[J]. J Controlled Release, 2001, 77(3): 261-272.
[134] Berthod F, Germain L, Li H, et al. Collagen fibril network and elastic system remodeling in a reconstructed skin transplanted on nude mice[J].Matrix Biol, 2001, 20(7):463-473.
[135] Miyata T, Taira T, Noishiki Y. Collagen engineering for biomaterial use[J]. Clin Mater, 1992, 9(3-4): 139-148.
[136]武继民,叶萍,孙伟建,等.胶原海绵及其止血性能的研究[J].生物医学工程学杂志, 1998, 15(1): 63-65.
[137] Rocha LB, Goissis G, Rossi MA. Biocompatibility of anionic collagenmatrix as scaffold for bone healing[J]. Biomaterials,2002, 23(2): 449-456.
[138] Ueda H, Hong L, Yamamoto M, et al. Use of collagen sponge incorporating transforming growth factor-b1 to promote bone repair in skull defects in rabbits[J]. Biomaterials, 2002, 23 (4):1003-1010.
[139] Lofthouse S, Nagahara S, Sedgmen B, et al. The application of biodegradable collagenminipellets as vaccine delivery vehicles in mice and sheep[J]. Vaccine, 2001, 19 (30): 4318-4327.
[140] Sheu MT, Huang JC, Yeh GC, et al. Characterization of collagen gel solutions and collagen matrices for cell culture [J]. Biomaterials, 2001, 22(13): 1713-1719.
[141] Mishima H, Okamoto J, Nakamura M, et al. Collagen activity of keratocytes cultured in a collagen matrix[J]. Jpn J Ophthalmol, 1998, 42(2): 79-84.
[142]王小燕,蔡继业,梁志红,等.应用原子力显微镜对不同来源Ⅰ型胶原蛋白溶液聚集行为的研究[J].山东生物医学工程,2002,21(4):17-20
[143]施辉阳.酶法提取生猪皮胶原的研究[D],生物化工,北京化工大学,2004
[144]贺建勋.水溶性聚丙烯酸酯涂饰剂[J],现代化工,1998,15(5): 40~41.
[145]王碧,王坤余,叶勇,等.水解胶原蛋白的溶解性和乳化性研究[J],皮革化工,2003,20(1):5-9
[146]田波,刘慧雯,于宏伟,等.大鼠胎脑神经细胞与几丁质多孔体、胶原蛋白海绵及明胶海绵生物相容性的实验研究[J],哈尔滨医科大学学报,2003,37(1):10-13
[147]周丽珍,陈玲,李琳,等.胶原蛋白的制备及用作生物医用材料的研究进展[J].中国医药工业杂志,2004,35(12):761-763
[148]张龙翔,张庭芳,李令媛等.生化实验方法和技术[M].北京:人民教育出版社,1991.112~118.
[149]肖和兰,孙素琴,周群,等.温度对胶原蛋白结构影响的二维红外相关光谱的研究[J].原子与分子物理学报,2003,20(2):211-218
[150]李国英,张忠楷,雷苏,等.胶原、明胶和水解胶原蛋白的性能差异[J],四川大学学报(工程科学版);2005,37(4):54-58
[151]李银清.梅花鹿茸胶原的分离提取及活性研究[D].长春;长春中医药大学,2007
[152]董万超,辛炎.梅花鹿茸和尾对大鼠性腺的影响[J]特产研究,1996,1
[153] Gelse K,Poschl E,Aigner T.Collagen-strcture,fuction,and biosynthesis[J].Adv Drug Delivery Rev,2003,55:1531
[154] Vogel WF.Collagen-receplor signaling in health and disease[J].Eur J Dermatol,2001,11:
[155] Yamaguchi Y,Mann DM,Ruoslathi E.Negative regulation of transforming growth facyor-βby the proteoglycan decorin[J].Nature,1990,346:281
[156] Hay ED.Extracellular matrix[J].J Cell Biol,1981,91:205
[157] Verrecchia F,Mauviel A.TGF-βand TNF-α:antagonistic cytokines controlling type1 collagen gene expression[J].J Cell Sig,2004,16:873
[158] Kuivaniemi H,Tromp G,Pmekop DJ.Mutations in collagen genes:causes of rare and some comnlton diseasesm in human[J]. FASEB J,199l,5:2052
[159] T. Landete-Castillejos, J.A. Estevez, A. Martínez, et al.Does chemical composition of antler bone reflect the physiological effort made to grow it[J], Bone, 2007,40(4):1095-1102
[160] JS Price, BO Oyajobi, ROC Oreffo, et al.Type X collagen and aggrecan expression in deer antler an in situ hybridization and immunocytochemical study[J],Bone, 1994,15(2):230
[161] Uwe Kierdorf, Ludek Barto,Treatment of the growing pedicle with retinoic acid increased the size of first antlers in fallow deer (Dama dama L.) [J],Toxicology and Endocrinology, 1999,124(1): 7-9
[162] Kyung-Ho Kim, Kap-Sung Kim, Byeong-Joon Choi, et al. Anti-bone resorption activity of deer antler aqua-acupunture, the pilose antler of Cervus korean TEMMINCK var[J]. Journal of Ethnopharmacology, 2005,96(3): 497-506
[163] Suk-Jong Suh, Kap-Sung Kim, A-Ram Lee, et al. Prevention of collagen-induced arthritis in mice by Cervus korean TEMMINCK var[J].Environmental Toxicology and Pharmacology, 2007,23(2),147-153
[164]徐叔云,卞如濂,陈修主编.药理实验方法学(第三版)[M].北京:人民卫生出版社,2006
[165]陈奇.中药药理实验方法[M].北京:人民卫生出版社,1994.
[166]林培英,潘竞锵.梅花鹿茸精对小鼠血清免疫球蛋白的影响[J].中成药,1984,12
[167]孙晓波,周重楚.鹿茸精对机体免疫功能的影响[J].中成药,1986,12(3),225～228.
[168]李万里,张合喜,田玉慧等.老年人尿钙氟锰镁和羟脯氨酸与骨密度的关系[J].新乡医学院学报,2000,17(3):153
[169]刘忠厚.骨质疏松学.科学出版社,2001,12
[170] Nuytinck L, Dalgleish R, Spotila L, et al. Substitution of glycine-661 by serine in theα1 andα2 chains of type I collagen results in different clinical and biochemical phenotypes[J].Hum Genet,1996,97:324-329.
[171] Struan FA,Ddavia M, Block G,et al. Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type Iα1 gene[J]. Nature genet,1996,14:203-205.
[172] Spotila LD.Mutation analysis of coding sequences for type I procollagen in individual with low bone density[J].J Bone Miner Res,1994,9:923-932.
[173] K. Kawana, M. Takahashi, H. Hoshino, K. Kushida. Comparison of serum and urinary C-terminal telopeptide of type I collagen in aging, menopause and osteoporosis[J].Clinica Chimica Acta, 2002,316:109-115.
[174] P. Garnero, and P. D. Delmas. An immunoassay for type I collagenα1 helicoidalpeptide 620-633, a new marker of bone resorption in osteoporosis[J].Bone.2003, 32: 20-26.
[175] Sam Shuster, Osteoporosis, a unitary hypothesis of collagen loss in skin and bone [J].Medical Hypotheses,2005,65:426-432.
[2]林鹤,曲晓波,王露菲,等.动物药整理研究(一)鹿茸,吉林中医药[J],2009,(1):50
[3]王本祥.鹿茸的研究[M].长春.吉林科学技术出版社1993:96-105
[4]严铭铭.人参鹿茸中蛋白多肽的纯化及活性研究[D].长春中医药大学,2007:5
[5]王玉.鹿茸化学成分的研究进展[J].吉林中医药,2006,26(12):73-75
[6]孟宪贞,程晓薇,陈力强.冷冻干燥与传统加工法制得的鹿茸化学成分分析极其比较研究[J],中国药房,1997,(8):3:110
[7]高士贤,中国动物药誌[M],吉林科学技术出版社,1996.10,963-976
[8]楼小红,陈建真.鹿茸中水溶性蛋白含量的测定[J].中国中医药科技,2003,10(1):31
[9]杨若明,张经华,张林源,等.麋鹿茸、马鹿茸和梅花鹿茸营养成分的分析比较研究[J],广东微量元素科学,2000,(7):12:47-51
[10]范玉琳,邢增涛,卫功庆,等.鹿茸蛋白的提取分离及其抗肿瘤活性[J].经济动物学报,1998;2(1):27-30
[11]周秋丽,郭颖洁.鹿茸多肤促进软骨和成骨样细胞增殖及骨折愈合[J].中国药理学报, 1999;20(3):279-282
[12]周秋丽,刘永强,王颖.梅花鹿茸和马鹿茸多肤化学性质及生物活性比较[J].中国中药杂志,2001;26(10):699-702
[13]周秋丽.鹿茸生长素药理作用的研究[J].中国药理学报,1997;11(5):16-19
[14]郭颖杰.鹿茸多肽对骨、软骨细胞增殖的实验研究[J].中国生化药物杂志,1998,19 (2) :74～75
[15]霍玉书,霍虹.鹿茸神经生长因子活性及促分化作用的研究[J].中药新药与临床药理, 1997;6(8):79-81
[16]张志强.鹿茸多肤的抗炎作用[J].中国药理学报,1994;15(3):282-284
[17]林冬云,鹿茸中活性多肽的研究[D],福州大学2004:6
[18]董万超,张秀莲,刘春华等.梅花鹿茸多肽新成分的提取分离及其生物学效应研究[J],特产研究,2000,2:7~10
[19]唐任能,赵雨,孙晓迪,等.梅花鹿鹿茸、鹿脱盘及鹿骨水溶性总蛋白比较研究[J],吉林中医药,2008,28(4):295-296
[20] Karpos,E.,Molnar,A.,Papp.,etal,Expression pattern of matrilins and other extracellular matrilins proteins characterize distinct stages of cell differentiation during antler development[J]. Matrix Biol,2005;24(2):124-135
[21] Barling,P.M.,Liu,H.,Matich,J.,et al. Expression of PTH/PTHrP receptor in growing red deer antler[J],Cell Biol lnt,2004;28(10):661-673
[22] Feng,J.Q.,Chen,D.,Esparza,J.,et al.Deer antler issue contains two types of bone morphogenetic protein 4 Mrna transcripts[J]. Biochim Biophys Acta ,1995;1263(2):163-168
[23] Feng,J.Q.,Chen,D.,Ghosh-Choudhury,N.,et al.Bone morphogenetic protein 2 transcripts in rapidly developing deer antler tissue contain an extended 5’non-coding region arising from a distal promoter[J].Biochim Biophys Acta,1997;1350(1):47-52
[24]王秋玉,王本祥.论鹿茸生长因子[J].中医药学报,2000,28(6):10-12
[25]崔昊震,尹明浩.鹿茸生长因子研究现状[J],延边大学医学学报,2006,3,29(1):70-72
[26] Ko,K.M.,Yip,T.T.,Tsao,S.W.,etal.Epidermal growth factor from deer(Cervus elaphus)submaxillary gland and velvet antler.GenComp Endocrinol[J], 1986;63(3):431-440
[27]李和平.中国茸鹿品种的鹿茸化学成分[J].东北林业大学学报,2003,7,31:(4)26-28
[28]杨秀伟,服部征雄,金子周司,等.日本生药学会第34回年会,1988:149~1535
[29]杨秀伟.花鹿茸、马鹿茸碱基成分的HPLC定量分析和其MA活性抑制作用[J].中草药,1995,26(l):17~19
[30]李继海,梅花鹿茸活性成分提取分离、功能评价及功能食品研究[D],中国农业大学,2005.4
[31]苗传风.梅花鹿茸磷脂和脂肪酸组成研究[J],特产研究1990,(3):48
[32]范玉琳.鹿茸化学成分研究的进展[J].中成药研究,1980,(1):23
[33]袁娟丽.鹿茸、麋鹿茸的化学和药理作用研究新进展[J] .江西中医学院学报,2003 ,6(15) ,2 :79～80
[34]杨秀伟,白云鹏.马鹿茸化学成分的研究[J] .中草药,1994 ,25(5) :229.
[35]龙远德,张惠祥,孙允秀.鹿茸中几种醚溶性成分的分离与鉴定[J].吉林大学自然科学学报. 1991(1) :1.
[36]高越,尹一子,李子健等.鹿茸中神经节苷脂的成分研究[J],吉林医学,2004,25(12):37-38
[37]熊和丽,杨鸣琦,杨萍等.梅花鹿鹿茸蛋白聚糖的提取与分离[J],西北农业学报,2007,16(4):80-82,91
[38]楼小红.吴巧凤.鹿茸中总糖的含量测定[J].中国药业,2003,12(2):57.
[39]蒋挺大.胶原与胶原蛋白[M],北京:化学工业出版社,第1版,2006:1-3;91-93;115-119
[40] Suttie,J.M.,et al. Velvet antler: A literature review. Batchelder[J],H.J.Health Supplement Retailer,1999;5:40-51
[41]王岩,金淑莉,陈晓光.鹿茸胶囊抗炎镇痛作用的研究[J].吉林中医药,2003,23(6):48
[42]刘青云.中药药理学[M],北京:人民卫生出版社,第二版,2002.2:258-260
[43]张红梅.人参与鹿茸配伍的作用机理研究[J],中医药学刊,2001,19(6):572
[44] Zheng,Z..Analysis on the therapeutic effect of combined use of acupuncture and mediation in 297 cases of male sterility[J].Jtradit Chin Med,1997;17(3):190-193
[45]楚立,张建平,李春花,等.H.S.B口服液的药理学研究[J].河北中医学院学报,1994;9(3):25-26
[46]刘筱茂.生津丹治疗男性不育104例[J],陕西中医学院学报,2000;23(2):35-36
[47]张红梅.人参与鹿茸配伍对肾阳虚大鼠生殖机能影响的实验研究[D].辽宁中医学院,2002.5
[48]洪文.针刺和鹿茸精穴位注射治疗肾阳虚男性不育症临床研究,广州中医药大学2002.6
[49]毋英杰,周丹,韩大庆等.诱发生长的雌鹿茸与雄鹿茸药理活性比较[J],特产研究,1996,(1):11-13
[50]何刚.鹿茸的药理作用与临床应用的研究进展[J].延边医学院学报,1992;(3):231-234
[51]楼一层,许健,程桃英.参茸百补胶囊的药效学研究[J],湖北中医学院学报,2003,5(2):23-24
[52] Wang Benxiang,Chen Xiaoguang. Inhibitory effect of hypoxanthine on monoamine oxidase activity.Acta Phamaceutica Sinica[J]. 1989:36(8):2-5.
[53]贺玉琢编译.汉方药对小鼠颌下腺生理活性物质的诱导作用及其作用机理[J],国外医学中国中药分册,1998,20(1):16-19
[54]许荔新,陈晓光.鹿茸口服液促进RNA和蛋白质合成作用的研究[J],中药药理与临床,2003;19(3)19-20
[55] Wang Benxiang,Chen Xiaoguang,et al.Influence of the active compounds isolated from pilose antler on syntheses of protein and RNA in mouse liver [J].Yao Xue Xue Bao,1990,25(5):321-325
[56] Wang Benxiang. Stimulating effects of deer antter extract on protein synthesis in senescence-accelerated mice in vivo [J]. Chem Pharm Bull, 1988,36(7):2593-2598
[57] Wang Benxiang,Chen Xiaoguang,et al. Effect of polyamines isolated from pilose antler (PASPA) on RNA polymerase activities in mouse liver [J].Yao Xue Xue Bao,1990;25(9):652-657
[58]杜中惠,曹际芬.鹿茸的临床应用及现代研究[J],中国药业,2000,9(1):53
[59]王岩,金淑莉,陈晓光.鹿茸胶囊耐缺氧和抗疲劳作用的实验研究[J].吉林中医药,2003;23(7):47-48
[60]姚克霓,补血生髓胶囊药理作用的研究[J],基层中药杂志,1996,10(3):35-36
[61]冯汉鸽,王喜云,张亚志.鹿茸不同部位的药理作用比较[J],时珍国药研究,1996,7(5):277-278
[62]孙晓波,周重楚.鹿茸精对机体免疫功能的影响[J].中成药研究,1986,21(8):636.
[63]乌恩,那顺·朝克图.鹿茸耐低氧作用的研究[J],内蒙古医学院学报,2007,29(3):192-193
[64]王羽竹,李子兰,贾瑞霞.牡丹江产鹿茸壮阳液药理实验研究[J].中国林副特产,2002,62(3):11-12
[65]关天颖,贾忠山,贾冬舒,等.特效生茸宝对小鼠造血功能和免疫功能的作用[J],中国兽医学报,199717(1):89-91
[66]王志华,赵文忠,李二秋.人参、鹿茸对体液免疫功能改善的研究[J],今日科技,2000(11):32-33
[67]唐巍然,于晓红,闻杰,等.鹿茸多糖对免疫功能低下模型小鼠细胞免疫功能的影响[J],中国中医药科技,2000,7(4):234.
[68]陈书明,聂向庭.鹿茸醇提物对白细胞减少小鼠模型腹腔吞噬细胞吞噬功能的影响[J],陕西中医学院学报,2000,1(1):4-5
[69]陈晓光,赵全成,邸琳,等.鹿茸糖肽对小鼠红细胞膜唾液酸酶的抑制作用[J],中国药理通讯,2003,20(3):24
[70]李召,鹿茸组分对人骨髓造血细胞体外增殖影响的研究[D],大连医科大学2006.6内科学
[71]关天颖,贾忠山,贾冬舒,等.特效生茸宝对小鼠造血功能和免疫功能的作用[J],中国兽医学报,199717(1):89-91
[72]王振宇,赵文静,李淑莲.鹿茸的药理作用及临床应用进展[J],中医药信息,2003,20(3):14
[73]葛迎春,李晨燕,任慧君,等.鹿茸提取物和人参皂甙对衰老细胞的琥珀酸脱氢酶和多糖含量的影响[J],特产研究,2001,(2):5-7.
[74]王立军,陈晓光,朴宪.鹿茸口服液对抗氧化酶的影响[J],中药药理与临床,2004,20(2):33-34
[75]关利新,初彦辉,郭艳芹,等.鹿茸抗衰老作用的研究[J],中国林副特产,1996,38(3):9-10
[76]王岩,陈晓光,金淑莉,等.鹿茸胶囊对青年及老年小鼠SOD活性的影响[J],中药实验药理,2003,31(4):22
[77]王本祥,陈晓光,徐惠波,等.次黄嘌呤-内源性单胺氧化酶(MAO)抑制剂样活性的研究[J],中药药理与临床,1996(1):9-14.
[78]陈书明,聂向庭.鹿茸醇提物抗氧化作用的实验研究,实验动物科学与管理[J],2000,17(1):22-24
[79]曲兆海,侯晓峰,刘景生.鹿茸对实验骨折愈合过程中TGF-β1的表达影响[J],中华实用中西医杂志,2003,3(16):707-709
[80]侯晓峰,李朝旭,刘景生.鹿茸对实验型骨折愈合中BMP-2表达的影响[J],辽宁中医杂志,2005,32(4):374-376
[81]周秋丽,王丽娟,郭颖杰,等.鹿茸多肽对实验性骨折的治疗作用及机理研究[J],白求恩医科大学学报,1999,25(5):586-588.
[82]郑洪新,任艳玲,杜松,等.活性鹿茸与热炸茸对去势大鼠骨质疏松症防治作用比较研究[J],中医药学刊,2004,22(4):616-619.
[83]陈晓超,柯李晶,陈躬瑞,等.鹿茸粗提液对大鼠成骨肉瘤细胞增殖的调节作用,中国中药杂志[J],2004,29(1):74-77
[84]姜廷良,霍海如,李兰芳,等.15中中西药物含药血清对大鼠成骨细胞增殖成熟的影响[J],中国骨质疏松杂志,2002,8(4):342-345.
[85]李娟,吴伟康,余克强.不同实验浓度补肾中药血清对人成骨细胞增殖及分化的促进作用[J],中国临床康复,2005,9(19):82-84
[86]张信岳,叶小弟,孟倩超,等.参茸强骨胶囊对皮质激素致大鼠骨质疏松症的保护作用[J],中国现代应用药学杂志,2003,20(4):265-268
[87]修忠标.鹿茸多肽对骨髓间质干细胞软骨分化生物学行为的影响[D],福建中医学院,中医骨伤科学,2005
[88]郭颖杰,周秋丽,刘平,等.鹿茸多肽对骨、软骨细胞增殖的实验研究[J],中国生化药物杂志,1998,19(2):74-76.
[89]侯建平,李丽静,王小丽,等.纳米鹿茸粗多肽对体外培养的软骨细胞代谢的影响[J],中国中医基础医学杂志,2006,12(7):555-556.
[90]修忠标,林建华.鹿茸多肽对人骨髓间质干细胞体外增殖的影响[J],福建中医学院学报,2005,15(1):34-37
[91]林建华,修忠标,吴朝阳,等.鹿茸多肽对兔骨髓间质干细胞体外增殖的影响[J],中华实验外科杂志,2005,22(7):827-828.
[92]林建华,修忠标,吴朝阳,等.鹿茸多肽对软骨表型化骨髓间充质干细胞凋亡的影响[J],中国修复重建外科杂志,2006,20(4):427-430
[93]修忠标,林建华,张春霞.鹿茸多肽对兔软骨细胞体外凋亡的影响[J],福建中医学院学报,2006,16(3):17-20.
[94]王利刚.中药鹿茸生长素对家兔关节软骨细胞代谢的影响[D],江西医学院,2001,骨科
[95]张志平,廖琦,李勇,等.鹿茸多肽对体外正常及凋亡软骨细胞代谢的影响[J],江西中医学院学报,2005,17(2):48-49
[96]陈东,孟晓婷.鹿茸多肽对胎大鼠脑神经干细胞体外诱导分化的实验研究[J].解剖学报,2004 ,6(3) :240– 242.
[97]翁梁,周秋丽.鹿茸多肽促进表皮和成纤维细胞增殖及皮肤创伤愈合[J].药学学报,2001 ,36(11) :817– 820.
[98]袁丽娟,谢金群.鹿茸、麋鹿茸的化学和药理作用研究新进展[J],江西中医学院学报,2003,15(2):79-80
[99]孟佳帆,王霞红,戎志毅,等.人源型可溶性胶原的研制[J],中国生物制品学杂志,2000,13(3):161-162
[100]刘秉慈.中国发明专利申请公开说明书.CN1081379A
[101]王新禾,张月娥,张锦生,等.人Ⅰ、Ⅲ型胶原的提取及其抗血清的制备[J],上海医科大学学报,1994,21(6):405-408.
[102]柴明胜,陈金国,叶仲贤,等.Ⅳ型胶原的提取纯化与抗血清的制备[J],陕西医学检验,1996,11(4):28-30
[103]姚敏捷,寇丽筠,王天成,等.人IV型胶原蛋白的提取及其单克隆抗体的制备与鉴定[J],细胞与分子免疫学杂志,1996,12(2):4-6
[104]李成章,樊明文.胚胎骨Ⅰ型胶原的提取与鉴定,生物化学与生物物理进展[J],1996,23(4):373-375
[105]范代娣,段明瑞,米钰,等.重组E.coli工程菌高密度培养生产人源型胶原蛋白,化工学报[J],2002,53(7):752-754
[106]王晓军,惠俊峰,米钰,等.重组类人胶原蛋白的分离纯化[J],中国生物制品学杂志,2003,16(4):212-214
[107]段明瑞,米钰,范代娣.重组人源型胶原蛋白基因工程菌补料分批发酵过程动力学研究化学反应工程与工艺[J],2002,18(3):238-243
[108]赵苍碧,黄玉东,李艳辉.从牛腱中提取胶原蛋白的研究[J],哈尔滨工业大学学报,2004,36(4)515-519.
[109]王由,李永岚,王维民.中国发明专利申请公开说明书.CN1407002A
[110]迪欧·弗兰[意大利].中国发明专利申请公开说明书.CN1110284A
[111]永井裕,藤本大三郎编著.胶原蛋白实验方法[M].刘平译.上海:上海中医学院出版社,1992.
[112]赵胜年.酶解鲜猪皮提取水解胶原蛋白的研究[J],食品工业科技,1998,(5):16-17
[113]李斯明,叶春婷,邹海燕,等.高纯度猪软骨Ⅱ型胶原的制备与检测[J],生物医学工程学杂志,2001,18(4):592-594
[114]林丁,刘兴明,李伟道,等.羊Ⅲ型前胶原放射免疫分析法的建立[J],生物技术,2002,12(2):33-34.
[115] KolodziejakaⅠ,Sikonski Z E,Njecikowaka C.Food Chem,1999,66(2):153-157.
[116]王瑾晔,董健.深海鱼皮组织工程用胶原蛋白和制备方法,中国发明专利申请公开说明书.NC1382806A
[117]鸿巢章二,桥本周久编.水产利用化学.郭晓峰,邹胜祥译.北京:农业出版社,1992
[118]郝林华,李八方.中国水产科学,1999,6(2):18-21
[119]方子季,梁东升,袁锦华.罗氏海盘车明胶代血浆的制备方法,中国发明专利申请审定说明书.CN1015776B.
[120]刘敬,许增禄,徐雁英,等.绝经后骨质疏松症病人Ⅰ型胶原的变化[J],解剖学报,2003,34(5):491-495
[121] Charles P, Mosekilde L,Risteli L, et al. Assessment of bone remodeling using biochemical indicators of type I collagen synthesis and degredation: relation to calcium kinetics[J].Bone Miner,1994, 24:81~94.
[122] Gertz BJ, Shao P, Hanson DA, et al. Monitoring bone resorption in early postmenopausal women by an immunoassay for crosslinked collagen peptides in wine[J].J Bone Min Res,1994,9:135~141.
[123] Fledelins C,Riis BJ, Overgaard K, et al. The diagnostic validity of urinary free pyridinolines to identify women at risk of osteoporosis[J]. Calcif Tissue Int,1994, 54:381~384.
[124] Cosman F, Nieves J, Wilkinson C,et al. Bone density change and biochemical indices of skeletal turnover[J].Calcif Tissue Int,1996, 58:236~243.
[125] Hoshino H, Takahashi M, kushida K,et al. Urinary encretion of type I collagen degradation products in healthywomen and osteoporotic patients with ventebral and hip fractures[J].Calcif Tissue Int,1998,62:36~39.
[126]李彦春,程宝箴,靳立强.胶原蛋白的应用[J].皮革化工,2002, 19(3):10-14.
[127]李彦春,靳立强,危东发,等.酶法提取牛皮胶原蛋白的研究[J].中国皮革, 2002, 31(2):6-9.
[128] Olsen D, Yang C, Bodo M, et al. Recombinant collagen and gelatin for drug delivery[J]. Adv Drug Deliv Rev, 2003, 55(12):1547-1567.
[129]林崇韬,文胡实,孙宏晨,等.乙酸溶解-酶消化法制备医用胶原膜[J].吉林大学学报(医学版), 2004, 30(1):75-78.
[130]李贺,刘白玲,陈华林,等.酶法提取猪皮胶原及其结构表征[J].中国皮革, 2002,31(23):14-16.
[131] NokelainenM, TuH, Vuorela A , et al. High-level production of human typeⅠcollagen in the yeast Pichia pastoris[J].Yeast, 2001,18(9):797-806.
[132] Friess W. Collagen-biomaterial for drug delivery[J]. Eur Jpharm Biopharm, 1998, 45(2): 113-136.
[133] Maeda M, KadotaK, Kajihara M, et al. Sustained release of human growth hormone(Hgh) from collagen film and evaluation of effect on wound healing in db/db mice[J]. J Controlled Release, 2001, 77(3): 261-272.
[134] Berthod F, Germain L, Li H, et al. Collagen fibril network and elastic system remodeling in a reconstructed skin transplanted on nude mice[J].Matrix Biol, 2001, 20(7):463-473.
[135] Miyata T, Taira T, Noishiki Y. Collagen engineering for biomaterial use[J]. Clin Mater, 1992, 9(3-4): 139-148.
[136]武继民,叶萍,孙伟建,等.胶原海绵及其止血性能的研究[J].生物医学工程学杂志, 1998, 15(1): 63-65.
[137] Rocha LB, Goissis G, Rossi MA. Biocompatibility of anionic collagenmatrix as scaffold for bone healing[J]. Biomaterials,2002, 23(2): 449-456.
[138] Ueda H, Hong L, Yamamoto M, et al. Use of collagen sponge incorporating transforming growth factor-b1 to promote bone repair in skull defects in rabbits[J]. Biomaterials, 2002, 23 (4):1003-1010.
[139] Lofthouse S, Nagahara S, Sedgmen B, et al. The application of biodegradable collagenminipellets as vaccine delivery vehicles in mice and sheep[J]. Vaccine, 2001, 19 (30): 4318-4327.
[140] Sheu MT, Huang JC, Yeh GC, et al. Characterization of collagen gel solutions and collagen matrices for cell culture [J]. Biomaterials, 2001, 22(13): 1713-1719.
[141] Mishima H, Okamoto J, Nakamura M, et al. Collagen activity of keratocytes cultured in a collagen matrix[J]. Jpn J Ophthalmol, 1998, 42(2): 79-84.
[142]王小燕,蔡继业,梁志红,等.应用原子力显微镜对不同来源Ⅰ型胶原蛋白溶液聚集行为的研究[J].山东生物医学工程,2002,21(4):17-20
[143]施辉阳.酶法提取生猪皮胶原的研究[D],生物化工,北京化工大学,2004
[144]贺建勋.水溶性聚丙烯酸酯涂饰剂[J],现代化工,1998,15(5): 40~41.
[145]王碧,王坤余,叶勇,等.水解胶原蛋白的溶解性和乳化性研究[J],皮革化工,2003,20(1):5-9
[146]田波,刘慧雯,于宏伟,等.大鼠胎脑神经细胞与几丁质多孔体、胶原蛋白海绵及明胶海绵生物相容性的实验研究[J],哈尔滨医科大学学报,2003,37(1):10-13
[147]周丽珍,陈玲,李琳,等.胶原蛋白的制备及用作生物医用材料的研究进展[J].中国医药工业杂志,2004,35(12):761-763
[148]张龙翔,张庭芳,李令媛等.生化实验方法和技术[M].北京:人民教育出版社,1991.112~118.
[149]肖和兰,孙素琴,周群,等.温度对胶原蛋白结构影响的二维红外相关光谱的研究[J].原子与分子物理学报,2003,20(2):211-218
[150]李国英,张忠楷,雷苏,等.胶原、明胶和水解胶原蛋白的性能差异[J],四川大学学报(工程科学版);2005,37(4):54-58
[151]李银清.梅花鹿茸胶原的分离提取及活性研究[D].长春;长春中医药大学,2007
[152]董万超,辛炎.梅花鹿茸和尾对大鼠性腺的影响[J]特产研究,1996,1
[153] Gelse K,Poschl E,Aigner T.Collagen-strcture,fuction,and biosynthesis[J].Adv Drug Delivery Rev,2003,55:1531
[154] Vogel WF.Collagen-receplor signaling in health and disease[J].Eur J Dermatol,2001,11:
[155] Yamaguchi Y,Mann DM,Ruoslathi E.Negative regulation of transforming growth facyor-βby the proteoglycan decorin[J].Nature,1990,346:281
[156] Hay ED.Extracellular matrix[J].J Cell Biol,1981,91:205
[157] Verrecchia F,Mauviel A.TGF-βand TNF-α:antagonistic cytokines controlling type1 collagen gene expression[J].J Cell Sig,2004,16:873
[158] Kuivaniemi H,Tromp G,Pmekop DJ.Mutations in collagen genes:causes of rare and some comnlton diseasesm in human[J]. FASEB J,199l,5:2052
[159] T. Landete-Castillejos, J.A. Estevez, A. Martínez, et al.Does chemical composition of antler bone reflect the physiological effort made to grow it[J], Bone, 2007,40(4):1095-1102
[160] JS Price, BO Oyajobi, ROC Oreffo, et al.Type X collagen and aggrecan expression in deer antler an in situ hybridization and immunocytochemical study[J],Bone, 1994,15(2):230
[161] Uwe Kierdorf, Ludek Barto,Treatment of the growing pedicle with retinoic acid increased the size of first antlers in fallow deer (Dama dama L.) [J],Toxicology and Endocrinology, 1999,124(1): 7-9
[162] Kyung-Ho Kim, Kap-Sung Kim, Byeong-Joon Choi, et al. Anti-bone resorption activity of deer antler aqua-acupunture, the pilose antler of Cervus korean TEMMINCK var[J]. Journal of Ethnopharmacology, 2005,96(3): 497-506
[163] Suk-Jong Suh, Kap-Sung Kim, A-Ram Lee, et al. Prevention of collagen-induced arthritis in mice by Cervus korean TEMMINCK var[J].Environmental Toxicology and Pharmacology, 2007,23(2),147-153
[164]徐叔云,卞如濂,陈修主编.药理实验方法学(第三版)[M].北京:人民卫生出版社,2006
[165]陈奇.中药药理实验方法[M].北京:人民卫生出版社,1994.
[166]林培英,潘竞锵.梅花鹿茸精对小鼠血清免疫球蛋白的影响[J].中成药,1984,12
[167]孙晓波,周重楚.鹿茸精对机体免疫功能的影响[J].中成药,1986,12(3),225～228.
[168]李万里,张合喜,田玉慧等.老年人尿钙氟锰镁和羟脯氨酸与骨密度的关系[J].新乡医学院学报,2000,17(3):153
[169]刘忠厚.骨质疏松学.科学出版社,2001,12
[170] Nuytinck L, Dalgleish R, Spotila L, et al. Substitution of glycine-661 by serine in theα1 andα2 chains of type I collagen results in different clinical and biochemical phenotypes[J].Hum Genet,1996,97:324-329.
[171] Struan FA,Ddavia M, Block G,et al. Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type Iα1 gene[J]. Nature genet,1996,14:203-205.
[172] Spotila LD.Mutation analysis of coding sequences for type I procollagen in individual with low bone density[J].J Bone Miner Res,1994,9:923-932.
[173] K. Kawana, M. Takahashi, H. Hoshino, K. Kushida. Comparison of serum and urinary C-terminal telopeptide of type I collagen in aging, menopause and osteoporosis[J].Clinica Chimica Acta, 2002,316:109-115.
[174] P. Garnero, and P. D. Delmas. An immunoassay for type I collagenα1 helicoidalpeptide 620-633, a new marker of bone resorption in osteoporosis[J].Bone.2003, 32: 20-26.
[175] Sam Shuster, Osteoporosis, a unitary hypothesis of collagen loss in skin and bone [J].Medical Hypotheses,2005,65:426-432.